Invasive lobular carcinoma of the breast; clinicopathologic profile and response to neoadjuvant chemotherapy over a 15-year period.

INTRODUCTION: Invasive lobular carcinoma (ILC) accounts for 5-15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile. METHODS: All patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile. RESULTS: A total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001). A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001). CONCLUSIONS: Atypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.

A multicentre review of the direct-access mammography programme in Ireland for women with breast pain.

AIM: To assess the current use of the direct access mammography pathway for breast pain and the rate of breast cancer detection in this patient cohort. MATERIALS AND METHODS: A retrospective review of general practitioner (GP)-referred mammograms performed during a 12-month period from January to December 2022 across four tertiary referral centres. With the use of medical records and GP referrals, patient demographics, presenting symptoms, family history, and clinical outcomes were recorded. RESULTS: The present study comprised 2,046 patients of which 21.6% did not report breast pain at the time of referral. Thirty-five per cent had a positive family history with 40% of these patients having no breast pain. Twelve per cent were recalled with 30% of these patients requiring biopsy. An overall cancer detection rate (CDR) of 7 per 1000 was determined for women with mastalgia. A CDR of 0 per 1,000 was determined for women <50 years with mastalgia alone and no additional risk factors for malignancy. Fisher's exact test showed no statistically significant association between breast pain and breast cancer. CONCLUSION: There was no statistically significant relationship found between breast pain and breast cancer. This review suggests a low cancer detection rate in women <50 years. In women <50 years with mastalgia without additional symptoms or family history, breast imaging is not required.

The association between breast density and breast cancer pathological response to neoadjuvant chemotherapy.

PURPOSE: Mammographic Density (MD) refers to the amount of fibroglandular breast tissue present in the breast and is an established risk factor for developing breast cancer. The ability to evaluate treatment response dynamically renders neoadjuvant chemotherapy (NACT) the preferred treatment option in many clinical scenarios. Previous studies have suggested that MD can predict patients likely to achieve a pathological complete response (pCR) to NACT. We aimed to determine whether there is a causal relationship between BI-RADS breast composition categories for breast density at diagnosis and the pCR rate and residual cancer burden score (RCB) by performing a retrospective review on consecutive breast cancer patients who received NACT in a tertiary referral centre from 2015 to 2021. METHODS: The Mann-Whitney U Test was used to test for differences between two independent groups (i.e. those who achieved pCR and those who did not). A binary logistic regression model was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for an association between the independent variables of molecular subtype, MD, histological grade and FNA positivity and the dependant variable of pCR. Statistical analysis was conducted with SPSS (IBM SPSS for Mac, Version 26.0; IBM Corp). RESULTS: 292 patients were included in the current study. There were 124, 155 and 13 patients in the BI-RADS MD category b, c and d, respectively. There were no patients in the BI-RADS MD category a. The patients with less dense breast composition (MD category b) were significantly older than patients with denser breast composition (MD category c, d) (p = 0.001) and patients who had a denser breast composition (MD category d) were more likely to have ER+ tumours. There was no significant difference in PgR status, HER2 status, pathological complete response (pCR), FNA positivity, or RCB class dependent upon the three MD categories. A binary logistic regression revealed that patients with HER2-enriched breast cancer and triple-negative breast cancer are more likely to achieve pCR with an OR of 3.630 (95% CI 1.360-9.691, p = 0.010) and 2.445 (95% CI 1.131-5.288, p = 0.023), respectively. CONCLUSION: Whilst dense MD was associated with ER positivity and these women were less likely to achieve a pCR, MD did not appear to independently predict pCR post-NACT.

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

PURPOSE: Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. METHODS: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. RESULTS: 963 pts. Mean age is 56 years. Mean tumour size is 1.7 cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. CONCLUSION: Over the 8 years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Value of a 21-gene expression assay on core biopsy to predict neoadjuvant chemotherapy response in breast cancer: systematic review and meta-analysis.

BACKGROUND: A recurrence score based on a 21-gene expression assay predicts the benefit of adjuvant chemotherapy in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This systematic review aimed to determine whether the 21-gene expression assay performed on core biopsy at diagnosis predicted pathological complete response (pCR) to neoadjuvant chemotherapy. METHODS: The study was performed according to PRISMA guidelines. Relevant databases were searched to identify studies assessing the value of the 21-gene expression assay recurrence score in predicting response to neoadjuvant chemotherapy in patients with breast cancer. The Newcastle-Ottawa Scale was used to assess the quality of the studies. Results are reported as risk ratio (RR) with 95 per cent confidence interval using the Cochrane-Mantel-Haenszel method for meta-analysis. Sensitivity analyses were carried out where appropriate. RESULTS: Seven studies involving 1744 patients reported the correlation between pretreatment recurrence score and pCR. Of these, 777 patients (44.6 per cent) had a high recurrence score and 967 (55.4 per cent) a low-intermediate score. A pCR was achieved in 94 patients (5.4 per cent). The pCR rate was significantly higher in the group with a high recurrence score than in the group with a low-intermediate score (10.9 versus 1.1 per cent; RR 4.47, 95 per cent c.i. 2.76 to 7.21; P < 0.001). A significant risk difference was observed between the two groups (risk difference 0.10, 0.04 to 0.15; P = 0.001). CONCLUSION: A high recurrence score is associated with higher pCR rates and a low-intermediate recurrence score may indicate chemoresistance. Routine assessment of recurrence score by the 21-gene expression assay on core biopsy might be of value when considering neoadjuvant chemotherapy in patients with ER-positive, HER2-negative breast cancer.

Meta-analysis of the cumulative risk of endometrial malignancy and systematic review of endometrial surveillance in extended tamoxifen therapy.

BACKGROUND: Optimal management of the endometrium in patients with oestrogen receptor-positive breast cancer taking extended tamoxifen therapy (for 10 years) remains uncertain. A meta-analysis was performed to determine the cumulative risk ratio (RR) for endometrial malignancy following extended compared with standard tamoxifen treatment. A systematic review was undertaken to identify whether routine endometrial surveillance in patients receiving tamoxifen is associated with earlier detection and reduced incidence of endometrial malignancy. METHODS: Two independent searches were undertaken in the Cochrane Library, PubMed and MEDLINE. A meta-analysis was performed of RCTs reporting on endometrial malignancy risk in extended tamoxifen therapy. A systematic review included prospective studies investigating the benefit of endometrial surveillance during tamoxifen therapy. RESULTS: Four RCTs reported on endometrial risk in extended tamoxifen therapy. The cumulative risk of endometrial malignancy increased twofold from 1·5 to 3·2 per cent with extended therapy compared with the standard 5 years of tamoxifen (RR 2·29, 95 per cent c.i. 1·60 to 3·28; P < 0·001). Four studies analysed the value of endometrial screening in 5-year cohorts. Endometrial cancer rates of up to 2 per cent were reported, which is higher than rates in the large extended tamoxifen trials. CONCLUSION: Extended adjuvant tamoxifen is associated with an increase in endometrial cancer. No clear benefit has been shown for routine endometrial surveillance in asymptomatic patients on tamoxifen therapy.

Role of bone scan in addition to CT in patients with breast cancer selected for systemic staging.

BACKGROUND: The majority of women with breast cancer present with localized disease. The optimal strategy for identifying patients with metastatic disease at diagnosis remains unclear. The aim of this study was to evaluate the additional diagnostic yield from isotope bone scanning when added to CT staging of the thorax, abdomen and pelvis (CT-TAP) in patients with newly diagnosed breast cancer. METHODS: All patients diagnosed with breast cancer who underwent staging CT-TAP and bone scan between 2011 and 2013 were identified from a prospective database of a tertiary referral breast cancer centre that provides a symptomatic and population-based screening breast service. Criteria for staging included: biopsy-proven axillary nodal metastases; planned neoadjuvant chemotherapy or mastectomy; locally advanced or inflammatory breast cancer and symptoms suggestive of metastases. RESULTS: A total of 631 patients underwent staging by CT-TAP and bone scan. Of these, 69 patients (10·9 per cent) had distant metastasis at presentation, with disease confined to a single organ in 49 patients (71 per cent) and 20 (29 per cent) having metastatic deposits in multiple organs. Bone metastasis was the most common site; 39 of 49 patients had bone metastasis alone and 12 had a single isolated metastatic deposit. All but two of these were to the axial skeleton. No preoperative histological factors identified a cohort of patients at risk of metastatic disease. Omission of the bone scan in systemic staging would have resulted in a false-negative rate of 0·8 per cent. CONCLUSION: For patients diagnosed with breast cancer, CT-TAP is a satisfactory stand-alone investigation for systemic staging.

A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic Preconditioning in Major Vascular Surgery.

A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed.

Peripheral artery disease: a marked lack of awareness in Ireland.

OBJECTIVES: Patients with symptomatic peripheral artery disease (PAD) have a 30% risk of death within 5 years. However, public awareness of vascular disease has been shown to be low. The aim of this study was to assess awareness regarding risk factors, significance and potential sequelae of PAD in an Irish population. DESIGN: A cross-sectional, anonymous survey of patients and members of the public. MATERIALS: An anonymous questionnaire was developed to collect details on basic demographics, presence of and treatment for risk factors for cardiovascular disease, awareness of PAD and its risk factors and sequelae. The local ethics committee granted ethical approval. METHODS: Two investigators in face-to-face interviews administered the survey with patients and members of the general public, older than 40 years of age, attending a range of outpatient clinics, day care services and in patients. RESULTS: A total of 336 questionnaires were administered. A post-secondary school course had been completed by 32% of respondents. Only 19% of patients reported familiarity with PAD, a figure considerably lower than those reporting familiarity with stroke (94%), coronary artery disease (78%) or diabetes (98%) (Chi Squared p<0.001). The only independent predictor of awareness of PAD was having a post-secondary school course with an odds ratio or 4.2. CONCLUSIONS: This study demonstrates a disturbing lack of awareness of PAD and highlight the need for a meaningful targeted public health awareness campaign on PAD in order to close the gap of knowledge in Irish patients, prior to any prevention campaign.

Predicting acute appendicitis? A comparison of the Alvarado score, the Appendicitis Inflammatory Response Score and clinical assessment.

BACKGROUND: Patients presenting with suspected appendicitis pose a diagnostic challenge. The appendicitis inflammatory response (AIR) score has outperformed the Alvarado score in two retrospective studies. The aim of this study was to evaluate the AIR Score and compare its performance in predicting risk of appendicitis to both the Alvarado score and the clinical impression of a senior surgeon. METHODS: All parameters included in the AIR and Alvarado scores as well as the initial clinical impression of a senior surgeon were prospectively recorded on patients referred to the surgical on call team with acute right iliac fossa pain over a 6-month period. Predictions were correlated with the final diagnosis of appendicitis. RESULTS: Appendicitis was the final diagnosis in 67 of 182 patients (37 %). The three methods of assessment stratified similar proportions (~40 %) of patients to a low probability of appendicitis (p = 0.233) with a false negative rate of <8 % that did not differ between the AIR score, Alvarado score or clinical assessment. The AIR score assigned a smaller proportion of patients to the high probability zone than the Alvarado score (14 vs. 45 %) but it did so with a substantially higher specificity (97 %) and positive predictive value (88 %) than the Alvarado score (76 and 65 %, respectively). CONCLUSIONS: The AIR score is accurate at excluding appendicitis in those deemed low risk and more accurate at predicting appendicitis than the Alvarado score in those deemed high risk. Its use as the basis for selective CT imaging in those deemed medium risk should be considered.

The impact of regional reconfiguration on the management of appendicitis.

BACKGROUND: Reconfiguration of surgical services in the Mid-West in 2009 resulted in a large increase in numbers of patients undergoing emergency surgery for appendicitis in University Hospital Limerick (UHL). AIMS: The aim of this study was to assess the impact of reconfiguration on the management of appendicitis in this area. METHODS: Data on all patients who underwent appendicectomy between January and June 2007 were compared with the corresponding data from January to June 2011. The numbers of operations, types of operations, lengths of stay (LOS), operation start times, rates of negative histology specimens and readmissions within 30 days were compared. One hundred and twenty-five appendicectomies [48 laparoscopic (38.4 %)] were performed in the 2007 group of which 32 specimens (25.6 %) were histologically negative. Three hundred and nineteen appendicectomies [238 laparoscopic (74.6 %)] were performed in the 2011 group of which 62 specimens (19.4 %) were histologically negative. The increase in numbers of laparoscopic procedures was significant (p < 0.001). The reduction in the negative appendicectomy rate was not statistically significant (p = 0.16). There were 10 conversions (20.8 %) to open surgery in the 2007 period and 12 (5 %) in the 2011 period (p = 0.001). Mean LOS for the 2007 and 2011 groups was 4.45 and 3.16 days (p < 0.001). Six (4.8 %) readmissions within 30 days occurred in the 2007 group with 20 (6.3 %) in the 2011 group (p = 0.66). CONCLUSION: Though reconfiguration of surgical services has resulted in a significant increase in workload, LOS has decreased significantly while maintaining acceptably low negative appendicectomy, conversion and readmission rates.

Purse-string approximation is superior to primary skin closure following stoma reversal: a systematic review and meta-analysis.

BACKGROUND: The incidence of surgical site infection (SSI) following stoma reversal can reach 40 %. A recent variation on primary linear closure (PLC) is purse-string approximation (PSA), where the skin is approximated via a purse-string suture but not closed. The optimal technique remains to be determined. The objective of this review was to compare outcomes with PLC versus PSA for skin closure following stoma reversal. METHODS: A literature search of Embase and Medline was performed to identify studies comparing PLC with PSA published between 1966 and 2012. Reviews of each study were conducted and data extracted. Random-effects methods were used to combine data, and between-study heterogeneity was assessed. RESULTS: Six out of 47 identified studies met the inclusion criteria: 2 randomized controlled trials and 4 case controlled series. For the primary outcome of SSI rate, 233 patients in the PLC and 170 patients in the PSA group were available for comparison. PSA resulted in a reduced rate of SSI (2.4 % PSA vs. 29.6 % PLC; OR 0.083, 95 % CI = 0.03-0.21, p < 0.001). No differences were noted in length of hospital stay. Three studies assessed self-reported cosmetic results at a minimum of 7 months post-operatively. Patients who underwent PSA reported greater satisfaction with the cosmetic outcome (Standard mean difference = 0.47 on ten-point scale, 95 % CI 0.15-0.79, p = 0.005). CONCLUSIONS: Purse-string approximation of stoma wounds is associated with an 80 % reduction in SSI with no negative effect on length of hospital stay or long-term cosmetic outcome.

Monitoring Clostridium difficile infection in an acute hospital: prevalence or incidence studies?

BACKGROUND: Surveillance of Clostridium difficile infection (CDI) is an essential component of a CDI preventative programme. AIMS: The aim of this study was to evaluate two methods of CDI surveillance. METHODS: Prevalence of CDI, antibiotic use and associated co-morbidity was assessed weekly on two wards over 6 weeks. In addition, CDI incidence surveillance was performed on all new CDI cases over a 13-week period. Cases were assessed for CDI risk factors, disease severity, response to treatment and outcome at 6 months. RESULTS: Clostridium difficile infection prevalence was 3.5% (range 2.9-6.1%) on the medical ward and 1.1% (range 0-3.5%) on the surgical ward. Patients on the medical ward were older and more likely to be colonised with MRSA; however, recent antibiotic use was more prevalent among surgical patients. Sixty-one new CDI cases were audited. Patients were elderly (mean age 71 years) with significant co-morbidity (median age adjusted Charlson co-morbidity score 5). CDI ribotypes included 027 (29 cases) 078 (5) and 106 (4). Eight patients developed severe CDI, seven due to 027. Antibiotic use was common with 56% receiving three or more antibiotics in the preceding 8 weeks. Twenty-four patients had died at 6 months, five due to CDI. CONCLUSION: Clostridium difficile infection prevalence gives a broad overview of CDI and points to areas that require more detailed surveillance and requires little time. However, patient-based CDI incidence surveillance provides a more useful analysis of CDI risk factors, disease and outcome for planning preventative programmes and focusing antibiotic stewardship efforts.

Patient and surgeon factors are associated with the use of laparoscopy in appendicitis.

AIM: The use of a minimally invasive approach to treat appendicitis has yet to be universally accepted. The objective of this study was to examine recent trends in Ireland in the surgical management of acute appendicitis. METHOD: Data were obtained from the Irish Hospital In-Patient Enquiry system for patients discharged with a diagnosis of appendicitis between 1999 and 2007. An anonymous postal survey was sent to all general surgeons of consultant and registrar level in Ireland to assess current attitudes to the use of laparoscopic appendectomy. RESULTS: The use of laparoscopic appendectomy increased throughout the study and was the most common approach for appendectomy in 2007. Multivariate analysis revealed age under 50 years (OR = 1.51), female sex (OR = 2.84) and residence in high-density population areas (OR = 4.15) as predictive factors for undergoing laparoscopic appendectomy in the most recent year of the study. While 97% of surgeons reported current use of laparoscopy in patients with acute right iliac fossa pain, in most cases it was selective. Surgeons in university teaching hospitals (42 of 77; 55%) were more likely to report using laparoscopic appendectomy for all cases of appendicitis than those in regional (six of 23; 26%) or general (13 of 53; 25%) hospitals (P = 0.048). CONCLUSION: This study has demonstrated a significant increase in laparoscopic appendectomy, yet a variety of patient and surgeon factors contribute to the choice of procedure. Differences in the perception of benefit of the laparoscopic approach amongst surgeons appears to be an important factor in determining the operative approach for appendectomy.

The management of right iliac fossa pain - is timing everything?

BACKGROUND: Right iliac fossa (RIF) pain remains the commonest clinical dilemma encountered by general surgeons. We prospectively audited the management of acute RIF pain, examining the relationship between symptom duration, use of pre-operative radiological imaging and patient outcome. METHODS: Over a six-month period, 302 patients, median age 18 years, 59% female, were admitted with RIF pain. Symptoms, clinical findings and laboratory results were documented. Patient management, timing of radiological investigations and operations, and outcome were recorded prospectively. RESULTS: Non-specific abdominal pain (26%), gynaecological (22%) and miscellaneous causes (14%) accounted for most admissions. Ultimately, 119 patients (39%) had appendicitis. Anorexia, tachycardia or rebound tenderness in the RIF significantly predicted a final diagnosis of appendicitis. Patients with perforated appendicitis (n = 29) had a longer duration of pre-hospital symptoms (median 50h) compared to those with simple appendicitis (median 17 h) (p<0.001). The use of pre-operative imaging resulted in an increased time to surgery but was not associated with increased post-operative morbidity or perforated appendicitis. CONCLUSION: The majority of patients presenting to hospital with RIF pain did not have appendicitis. Increased duration of pre-hospital symptoms was the main factor associated with perforated appendicitis. However, increased in-hospital time to theatre was not associated with perforated appendicitis or post-operative morbidity.

Management and outcome in patients following head injury admitted to an Irish Regional Hospital.

PRIMARY OBJECTIVE: Each year in Ireland, 11 000 patients are admitted to hospital with a traumatic brain injury (TBI) but there are no data on subsequent disability in such patients. The objective of this study was to assess the management and outcome in patients of working age admitted with TBI to the unit. METHODS: Two hundred and sixteen patients admitted with TBI aged 16-65 were identified. Self-reported incidence of disability and access to appropriate services was assessed using the Glasgow outcome scale and a problem-orientated questionnaire. RESULTS: Eighty-five per cent of patients eligible for review agreed to participate. The majority of injuries (86%) were mild. An intracranial injury was identified on 35% of CT brain scans performed. Patients with an abnormality on CT scanning were more likely to report difficulties with headache, concentration and memory at time of follow-up. When questioned, 34% of patients still perceived difficulties since their injury. Of this group, 60% didn't receive any input from rehabilitation services. One year post-injury, 11% of patients remained unfit for work. CONCLUSION: A significant number of patients, even with mild TBI, continue to suffer sequelae from their injury augmented by difficulty in accessing appropriate rehabilitation services.

The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers.

Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition. Since, in animals, LI is disrupted by amphetamines and enhanced by antipsychotics, LI disruption has been proposed as a measure of the characteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupted LI in healthy volunteers, and LI was normal in non-medicated patients with schizophrenia, the previous findings in schizophrenic patients were entirely due to the negative effects of their medication on LI (Williams et al., 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test performance (spatial working memory (SWM), Tower of London and intra/extra dimensional shift, from the CANTAB test battery) and visual analogue rating scales, were also included as other measures of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding may be explained by increased distractibility which was indicated by an increase in antisaccade directional errors in this group. In contrast, LI was significantly increased by chlorpromazine but not by an equally sedative dose of lorazepam (both drugs causing marked decreases in peak saccadic velocity). Paroxetine had no effect on LI, eye movements or CANTAB neuropsychological test performance. Haloperidol was associated with impaired SWM, which correlated with the degree of dysphoria/akathisia, but no other drug effects on CANTAB measures were detected. We conclude that the effect of antipsychotics on LI is both modality and pharmacologically dependent and that further research using a wider range of antipsychotic compounds is necessary to clarify the cognitive effects of these drugs, and to determine whether there are important differences between them.